In our study, NSUN4 was screened as a potential regulator through conjoint analysis of the single‐cell transcriptome and m5C epitranscriptome in SLE patients, which was significantly upregulated in the CD7highCD74high T cell subcluster and positively regulated CD74 mRNA stability and CD8+T cell exhaustion by regulating mitophagy in vitro. Here, NSUN4 is linked to systemic lupus erythematosus.